Featured Research

from universities, journals, and other organizations

New class of brain-protecting drugs emerging

Date:

January 31, 2010

Source:

Emory University

Summary:

The compound 7,8-dihydroxyflavone mimics BDNF, one of the brain's own growth factors, and can protect brain cells against damage in animal models of seizure, stroke and Parkinson's disease. 7,8-dihydroxyflavone is a member of a family of antioxidant compounds naturally found in foods ranging from cherries to soybeans.

Related Articles

7,8-dihydroxyflavone is a member of the flavonoid family of chemicals, which are abundant in fruits and vegetables. The compound's selective effects suggest that it could be the founder of a new class of brain-protecting drugs.

The results were published online in the Proceedings of the National Academy of Sciences.

Investigators at Emory University School of Medicine, led by Keqiang Ye, PhD, associate professor of pathology and laboratory medicine, were searching for a way to mimic a protein found in the brain called BDNF (brain-derived neurotrophic factor).

"BDNF has been studied extensively for its ability to protect neurons vulnerable to degeneration in several diseases, such as ALS, Parkinson's and Alzheimer's disease," Ye says. "The trouble with BDNF is one of delivery. It's a protein, so it can't cross the blood-brain barrier and degrades quickly."

Working with Ye, postdoctoral fellow Sung-Wuk Jang sifted through a library of chemicals to find those that could stimulate one of the proteins on the surfaces of neurons that BDNF binds to. They could show that 7,8-dihydroxyflavone sends survival signals to brain cells by pulling together two TrkB receiver-dish molecules, just like BDNF does.

Moreover, it is active in the brain when injected into the body cavity, meaning that it can cross the blood-brain barrier. Ye says many experimental "neuroprotectant" drugs have been unsuccessful in clinical trials for diseases such as stroke and Parkinson's over the last decade.

"What's different is this is a new pathway, offering us new opportunities," he says. "This is the first molecule we've found that specifically triggers TrkB."

7,8-dihydroxyflavone could partially prevent the death of neurons in experimental models of three neurological diseases:

Seizure: Mice treated with the stimulant kainic acid

Stroke: Loss of blood flow induced in mice by blocking a cerebral artery

Parkinson's disease: Mice treated with a toxin that kills the same neurons affected by Parkinson's

To show that the effects of 7,8-dihydroxyflavone depended on TrkB, the authors used mice with a modified TrkB gene, which makes their neurons vulnerable to a chemical that is not otherwise toxic. That chemical could inhibit the effects of 7,8-dihydroxyflavone.

7,8-dihydroxyflavone is a member of a family of antioxidant compounds naturally found in foods ranging from cherries to soybeans. Tests in animals indicate that the compound has low chronic toxicity, Ye says. In clinical trials, BDNF itself can have side effects such as sensory alterations, weight loss or nausea.

"It is likely that many people take in small amounts of 7,8-dihydroxyflavone in their diets," Ye says. "But drinking green tea or eating apples doesn't give you enough for a sustained effect."

In the initial screening process, several flavonoid compounds had similar properties to 7,8-dihydroxyflavone. Ye says his laboratory has already identified compounds that are several times more active. The next step is more animal studies to choose compounds likely to have the best drug profiles: stable and non-toxic.

Manuel Yepes, MD, assistant professor of neurology at Emory University School of Medicine, and his colleagues performed the stroke model experiments. Gary Miller, PhD, associate professor in Emory's Rollins School of Public Health, and his colleagues performed the Parkinson's-simulating toxin experiments.

Investigators from Georgia State University, UCLA, and the Centers for Disease Control and Prevention contributed to the research, which was supported by the National Institutes of Health.

Featured Research

Mar. 31, 2015  Researchers have illuminated an important distinction between mice and humans: how human livers heal. The difference centers on a protein called PPAR alpha which activates liver ... full story

Mar. 31, 2015  Researchers have recorded the first direct observations of the micro-scale mechanisms behind the ability of skin to resist tearing. The results could be applied to the improvement of artificial skin, ... full story

Mar. 31, 2015  Fewer than half of the physicians trained in the United States in 2013 received formal education or training on the subject of exercise, according to new research. "There are immense medical benefits ... full story

Mar. 31, 2015  Memory and as well as connections between brain cells were restored in mice with a model of Alzheimer's given an experimental cancer drug, researchers report. "With this treatment, cells under ... full story

Mar. 31, 2015  Increasing state alcohol taxes could prevent thousands of deaths a year from car crashes, say researchers, who found alcohol-related motor vehicle crashes decreased after taxes on beer, wine and ... full story

Mar. 31, 2015  Alcoholism takes a toll on every aspect of a person's life, including skin problems. Now, a new research report helps explain why this happens and what might be done to address it. "The clinical ... full story

Mar. 31, 2015  A new population of 'memory' immune cells has been discovered by scientists, throwing light on what the body does when it sees a microbe for the second time. This insight, and others like it, will ... full story

Mar. 31, 2015  Coronary heart disease and stroke, two of the leading causes of death in the United States, are diseases associated with heightened platelet reactivity. A new study in humans suggests an underlying ... full story

Mar. 31, 2015  A new study had researchers seeking answers to why the therapeutic benefit afforded by SSRIs was so limited in children and teenagers. If researchers can uncover the biological mechanisms preventing ... full story

Featured Videos

Solitair Device Aims to Takes Guesswork out of Sun Safety

Reuters - Innovations Video Online (Mar. 31, 2015)  The Solitair device aims to take the confusion out of how much sunlight we should expose our skin to. Small enough to be worn as a tie or hair clip, it monitors the user&apos;s sun exposure by taking into account their skin pigment, location and schedule. Matthew Stock reports.
Video provided by Reuters

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015)  Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline.
Video provided by Washington Post

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015)  Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17
Video provided by AFP

Related Stories

Apr. 2, 2013  Biologists in Germany have explored how to protect neurons that control movements from dying off. In a new paper, they report that the molecule 7,8-Dihydroxyflavone, also known as vitamin P, ensures ... full story

July 11, 2011  Stroke is a leading cause of long-term disability and death in the United States. New research has now identified a way to exploit one of the brain's self-repair mechanisms to protect nerve ... full story

Jan. 12, 2011  Living a traumatic experience favors the persistence of fear associated with an aversive stimulus, known as fear conditioning. Scientists in the US and Spain have now found that such an effect, in ... full story

Dec. 7, 2010  Investigators have discovered a family of small molecules that shows promise in protecting brain cells against nerve-degenerative diseases such as Parkinson's, Alzheimer's and ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.